KEY TAKEAWAYS
- The study aimed to investigate TPT1-AS1’s role in OC progression, focusing on its impact on ferroptosis and protein interactions.
- Researchers noticed that TPT1-AS1 drives OC progression by inhibiting ferroptosis and interacting with CREB1 and KHDRBS3.
Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes, with dysregulation implicated in various diseases, including cancers. The lncRNA TPT1-AS1 (TPT1 Antisense RNA 1) promotes tumor progression in several cancers, including ovarian cancer (OC), but its influence on ferroptosis and interaction with other proteins remains underexplored.
Lei Cao and the team aimed to assess the role of TPT1-AS1 in regulating ferroptosis in OC cells and to elucidate the underlying molecular mechanisms.
They performed an inclusive analysis to investigate the functional significance of TPT1-AS1 in OC. Patients’ OC specimens and cell lines were analyzed to assess TPT1-AS1 expression levels using RT-qPCR, in situ hybridization (ISH), and fluorescence in situ hybridization (FISH) assays. Functional assays were conducted to evaluate the impact of TPT1-AS1 knockdown on cell proliferation, migration, invasiveness, and cell cycle progression in OC.
Additionally, the interaction of TPT1-AS1 with other proteins was explored and validated using bioinformatics approaches. The involvement of TPT1-AS1 in erastin-induced ferroptosis was further investigated by employing Iron Assay, Malondialdehyde (MDA) assay, and reactive oxygen species (ROS) detection techniques.
They founded that TPT1-AS1 overexpression in OC was correlated with an unfavorable prognosis. TPT1-AS1 knockdown led to the suppression of cell proliferation, migration, and invasiveness. Moreover, TPT1-AS1 was found to inhibit erastin-induced ferroptosis, and in vivo experiments confirmed its oncogenic impact on tumor development.
Mechanistically, TPT1-AS1 was discovered to regulate Glutathione Peroxidase 4 (GPX4) transcription via CREB1 (cAMP response element-binding protein 1) and to interact with the RNA-binding protein KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) to modulate CREB1.
The study concluded that TPT1-AS1 promotes OC progression by inhibiting ferroptosis and upregulating CREB1, forming a regulatory axis with KHDRBS3. These findings highlight the complex regulatory network involving long non-coding RNAs (lncRNAs), RNA-binding proteins (RBPs), and transcription factors in cancer progression.
No funding information for this study was given.
Source: https://pubmed.ncbi.nlm.nih.gov/39141012/
Cao L, Wang Y, Liu J, et al. (2024). “Long non-coding RNA TPT1-AS1 inhibits ferroptosis in ovarian cancer by regulating GPX4 via CREB1 regulation.” Am J Reprod Immunol. 2024 Aug;92(2):e13864. doi: 10.1111/aji.13864. PMID: 39141012.
